Methanol → 6-(3-Acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acid

HRID 232458노트

반응식

HRID 232458 반응식
CO.[C:3]([NH:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]([F:22])=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[C:14]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])[N:13]=2)[CH2:8]1)(=[O:5])[CH3:4].[OH-].[Na+]>O.C(OCC)(=O)C>[C:3]([NH:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]([F:22])=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[C:14]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])[N:13]=2)[CH2:8]1)(=[O:5])[CH3:4]

참가 물질

6

반응물 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 13821764Methyl 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate

생성물 1

HCID 138217726-(3-Acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acid수율 93%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8857Ethyl Acetate용매

실험 절차

In a mixture of 30 ml of tetrahydrofruran, 10 ml of methanol and 4 ml of water was suspended 980 mg of methyl 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinate, and 5.3 ml of 1N aqueous sodium hydroxide solution was added thereto, after which the resulting mixture was subjected to reaction at 65° C. for 3 hours. Subsequently, the reaction mixture was added to a mixture of 50 ml of ethyl acetate and 50 ml of water, and the aqueous layer was separated, after which the pH thereof was adjusted to 2.0 with 1N hydrochloric aicd. The crystals thus deposited were collected by filtration and washed successively with 2 ml of water and 2 ml of ethanol to obtain 880 mg (yield 93.0%) of 6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinic acid having a melting point of 232°-234° C.

후처리

  1. additionwas added
  2. customafter which the resulting mixture was subjected to reaction at 65° C. for 3 hours
  3. customthe aqueous layer was separated
  4. filtrationThe crystals thus deposited were collected by filtration
  5. washwashed successively with 2 ml of water and 2 ml of ethanol

출처 및 근거

ORD 기록
ord-35201cdc06fc4903b1e21af25c883aab
출처 데이터셋
uspto-grants-1989_07
특허 번호
US04851535

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